Mice infected with the diabetogenic D variant of EMC virus developed some of the long-term complications of diabetes, including diffuse and nodular glomerulsclerosis, an increase in the thickness of the glomerular basement membrane, mild retinal changes, and a four- to six-fold increase in mortality. Thus, animals infected with the diabetogenic variant of EMC virus develop both the early metabolic changes and at least some of the long-term complications of insulin-dependent diabetes. The nondiabetogenic B variant of EMC virus is antigenically similar to the diabetogenic D variant of this virus. Immunization of mice with the nondiabetogenic B variant completely prevented the development of diabetes in mice subsequently challenged with the diabetogenic D variant. Thus, at least in mice, virus-induced diabetes can be completely prevented by a live, attentuated vaccine. Reovirus type 1 triggers an autoimmune polyendocrine disease characterized by transient diabetes and growth retardation. This syndrome can be prevented by immunosuppression.